5-phosphomethyl derivatives of 6-chromanols and processes for preparing same



United States Patent Otfice 3,-ihhfi38 Patented Dec. 8, 1964 Thisinvention relates to substituted methyl derivatives of 1,4-quinones andtheir corresponding -chromanois. More particularly, it is concerned withS-phosphorne-thyl derivatives of 6-chromanols and processes andintermediates for their synthesis from appropriately substituted1,4-quinones.

Oxidative phosphorylation is an essential reaction in the respiratorysequence of most living tissue. In this process, energy is stored by thebiosynthesis of ATP and released by the heterolytic cleavage of theactive phosphate moiety of ATP. For the biosynthesis of ATP,

low energy phosphate must be converted to high energy 2 phosphate priorto its reaction with ADP-to form ATP. The compounds of this inventionappear to participate in metabolic processes involving hydrogentransport and coupled phosphorylation; in this process, low energyphosphate is converted oxidatively to a form of high energy phosphate.The phosphates of this invention on oxidation could yield activephosphate for these metabolic conversions.

It is an object of this invention to provide new 5- phosphomethylderivatives of 6-chrornanols and processes for their preparation.Another object is to provide new S-halornethyl derivatives of6-chromanols and processes for their preparation. A further object is toprovide methods of converting S-halomethyl derivatives to thecorresponding S-phosphomethyl derivatives of the chromanols. Stillanother object is to provide a method for the direct conversion ofy-hydroxy derivatives of 2,3-dimethoxy-S-methyl-6-alkyl-1,4-benzoquinones to the correspondingS-phosphomethyl--chromanols. other objects of our invention will beapparent from the detailed description of this invention hereinafterprovided.

In accordance with an embodiment of this invention, the 'y-hydroxy sidechain substituted derivatives (I) of the 1,4-quinones are reacted withan acyl halide to produce the corresponding 5-chloromethyl-6-chromanylacylates (II). The latter compounds are then reacted with a silverphosphate ester such as silver dibenzyl phosphate to produce thecorresponding 5-phosphomethyl triester derivatives (III). The phosphatederivatives are then selectively reduced to cleave two of the estergroups of the phosphate moiety and yield the 5-phosphomethyl-6-chrornanyl acylates (IV) which may be further selectively hydrolyzed toproduce the corresponding S-phosphornethyl-fi-chromanols (V). Thesereactions can be shown structurally as follows:

These and g 3/0 CHzCaHs CHzOP Z{ In the above flow sheet, Z representson o- CH3- X represents halogen, R represents an acyl radical and Rrepresents methyl or wherein n represents an integer from one to nine.Thus, these reactions can be carried out with the 'y-hydroxy side chainsubstituted derivative of vitamin K; of the formula 1 a compound of thecoen zyrne Q series having the formula v .3) wherein n is an integerfrom zero to nine, or a vitamin E derivative of the formula These'y-hydroxy side chain substituted derivatives of vitamin K and thecoenzyme- Q- series can be prepared in accordance with proceduresdescribed in copending application Serial No. 266,202 filed March 19,1963.

The first step of this above-described procedure is carried out bymixing the 'y-hydroxy derivative (I) with an acyl halide and allowingthe reaction mixture to stand at room temperature for sufficient time toconvert the 'y-hydroxy compound to the desired S-chloromethyl-G- acylate(II). While various acyl halides can be used for this reaction, it ispreferred to utilize a lower alkanoyl chloride or bromide such as acetylchloride, propionyl bromide, propionyl chloride and the like. Aftercompletion of the reaction, the desired reaction product is recovered bypouring the reaction mixture onto ice, extracting the aqueous solutionwith ether and evaporating the dried ether extract.

The second step of the process is effected by reacting the S-halomethylcompound (II) with silver dibenzyl phosphate in a suitable solvent forthe halomethyl compound such as benzene, toluene, acetonitrile and thelike and refluxing the resulting reaction mixture for sui'ficient timeto complete the formation of the desired triester. This product can berecovered by filtering the reaction mixture to remove the silverchloride, washing the filtered solution with water and concentrating thedried solvent under reduced pressure.

The benzyl groups of the triphosphate (III) so obtained can be cleavedby hydrogenolysis under mild conditions, for example, by reaction withhydrogen in the presence of a a hydrogenation catalyst such a noblemetal in a suitable solvent medium such as ethanol, dioxane and thelike. After completion of the reaction, the dihydrogenphosphate (IV) canbe recovered by removing the catalyst and by evaporating, the solvent.The dihydrogenphosphate (IV) so obtained is an acidic substance formingsalts with alkalis and other basic substances. It is converted to thecorresponding -phosphomethyl-6-chromanol (V) by selective hydrolysis.

Thus, in accordance with the above-described procedures, the y-hydroxyside chain substituted derivative of vitamin K, of vitamin E, and of2,3-dimethoxy-5-methyl- 6-alkyl-1,4-benzoquinones such as2,3-dimethoxy-6-(3-hydroxy-3-methylbutyl)-5-methyl-1,4-benzoquinone,2,3-dimethoxy-6-(3-hydroxy-3,7,11,15 tetramethylhexadecyl)-S-methyl-l,4-benzoquinone, 2,3-dimethoxy-6-(3-hydroxy-3,7,11,15,19,23,27,31,35,39 decamethyltetracontyl) 5-methyl-1,4-benzoquinone, and the like are converted to the corresponding5-phosphornethyl-6-chromanol.

Alternatively, and in accordance with a further embodiment of thisinvention, the S-phosphomethyl-6-chromanols of the2,3-dimethoxy-5-methyl-6-alkyl-1,4-benzoquinones can also be obtained byreacting the corresponding 'yhydroxy substituted side chain derivativewith phosphoric acid.

The following examples illustrate specific methods of carrying out thevarious processes of the. present invention.

Example 1 5-chl0r0methyl-3,4-dihydr0-2-methyl 2 (4,8,12trimethyltridecyl)-2-H-naphtho[1,2-[2-1 pyran-6-yl acetate. Three gramsof 3-(3-hydroxy-3,7,11,15-tetramethylhexa- 4idecyl)-2-methyl-1,4-naphthoquinone is reacted with 15 ml. of acetylchloride. The reaction mixture is protected from atmospheric moistureand allowed to stand at room temperature overnight. The mixture waspoured onto ice, and the product extracted with ether. The extract isWashed with water, dried over anhydrous magnesium sulfate andconcentrated, and the product purified by chromatography on 2 00 g. ofsilica gel packed in n-hexane. After impurities are eluted from thecolumn with 1% ether in n-hexane, 5-chlorometl1yl-3,4-dihydro-2-methyl-2-(4,8,12-trimethyltridecyl)-2-H-naphtho[ 1,2-b l pyran 6- 'yl acetateis eluted with 3% ether in n-hexane. The product was characterized byNEW 248 mp (E% 707); an; 3.4 5.65 1

The 3-(3-hydroxy-3,7,11,l5,-tetramethylhexadecyl) 2-methyl-1,4-naphthoquinone used as the starting material can be preparedas follows:

An ice cold mixture of 2.2 g. of vitamin K (2-'methyl-E-phytyl-l,4-naphthoquinone), in 20 ml. of concentratedsulfuricacid is stirred until it becomes homogenous. The solution iskept ice cold for about an hour and then poured onto ice. The product isextracted with ether, and the extract washed with water, dried overanhydrous magnesium sulfate and concentrated in vacuo. The residual oil(2.2 g.) is purified by chromatography on a column of 230 g. of silicagel packed in n-hexane. After preliminary elution using n-hexane andn-hexane containing 1%, 3% and 10% ether, the product is eluted withn-hexane containing 25% ether. The eluate is concentrated and theresidue is purified by chromatography on 200 g. of silica gel andelution with n-hexane. From the eluate,3-(3-hydroxy-3,7,11,15-tetrarnethylhexadecyl)-2-rnethyl-1,4-naphthoquinone is obtained. The product is characterizedby Mitt? 325 m (117% 58), 273 m (E% 375), 264 mp. (13% 366), 249 mu (E%398), 244 mu (E% 380); it-3;. M,

Example 2 5 chloromethyl 7,8-dimethoxy-2,2-dimethyl-6-chr0- many!acetale.Two hundred milligrams of 2,3-dimethoxy 6(3-hydroxy-3-methylbutyl)-5-methyl-1,4-benzoquinone is dissolved in 1ml. of acetyl chloride and allowed to react in the absence of moisturefor sixteen hours at room temperature. The reaction mixture is pouredonto ice arid extracted with ether; the extract being washed with waterand dried over magnesium sulfate. The ether is evaporated at reducedpressure leaving a yellow oil which crystallizes on standing. Pure 5-chloromethyl 7,8-dimethoxy-2,Z-dimethyI-G-chromanyl acetate, M.P. 8284C., is obtained by recrystallization of the reaction product from coldmethanol.

The 2,3 dimethoxy 6-(3-hydroxy-3-methylbutyl)-5- methyl-1,4-benzoquinoneused as the starting material in the above example is prepared asfollows:

Two hundred and fifty milligrams of the 6-chromanol of coenzyme Q (7,8dimethoxy-2,2,5-trimethyl-6-chromanol), is dissolved in 30 ml. of ether,and a mixture of 10 ml. of 5% ferric chloride in ethanol and 10 ml. ofwater is added slowly with rapid stirring. The reaction mixture isdiluted with water and the layers separated. The ether solution iswashed with water until neutral, and then dried over magnesium sulfate.Evaporation. of the ether yields 2,3dimethoxy-G-(3-hydroxy-3-methylbutyl) 5-methyl-1,4-benzoquinone. It ischaracterized by A of 275-280 mg.

Example 3.

5 chloromethyl-8,7-dimethoxy-2-methyl-2-(4,8,12-triniethyltridecyl)-6-chromanyl acetate.--A solution containing 206 mg. of2,3-dimetho-xy-6-(3-hydroxy-3,7,11, 15tetramethylhexadecyl)-5-meth.yl-l,4-benzoquinone in 10 ml. of acetylchloride is allowed to stand at room temperature for 20 hrs. Thesolution is poured onto about us 292 ml (En... 7 4) An analytical sampleis prepared by column chromatography. The produce is absorbed from anisooc-tane solution onto 25 g. of silica gel packed in isooctane. Thecolumn is washed with isooctane, and then eluted with ether-isooctane(5:95) giving of the pure compound:

ma 293 mu (n tmasz up: 5.64 6.30 8.3 and 8.99

The nuclear magnetic resonance spectrum is in accord with the structure.p I

The 2,3-dimethoxy-6 (3-hydroxy-3,7,11,15-tetrmethylhexadecyl)-5-methyl-1,4-benzoquinone used as the startingmaterial in this example can be prepared as follows:

To a solution containing 5v g. of the 6-chromanol of hexahydrocoenzymeQ.,[7,8 dimethoxy-2,5-dinrethyl-2- .(4,8,12trimethyltridecyl)-6-chromano1] in 185 ml. of

new 276 ml (Eu... 2 2) An analytical sample is prepared by columnchromatography. One gramof the product is absorbed from an isooctanesolution onto 1 g. of Florisil packed in'isooctane. The columnis washedwith ethanol-isooctane (1:99), and then the product is eluted withethanol-isooctane (3:97) giving 2,3-dimethoxy-6-(3-hydroxy-3,7,l1,IS-tetramethyldexadecyl) --methy1-1,4-benzoquinone,

Mar 276 mu. ($1 ,325); x3e; 2801s, 6.06;, 6.21 7.90 8.30 and 8.63

The nuclear magnetic resonance spectrum is consistant with thestructure.

Example 4 0,0 dibenzyl O-{6-acet0*xy-3,4-dihydro-Z-methyl-Z- (4,8,12trimethyltridecyl) Z-H-naphzho[1,2-b1pyran-5- ylmethyl} ph0spha2e.Amixture of 780 mg. of S-chloromethyl3,4-dihydro-2-methyl-2-(4,8,l2-trimethyltridecyl)-2-H-naphtho[1,2b]pyran-6-ylacetate, 780 mg. of silver dibenzyl phosphate and 40 ml. ofacetorn'trile is refluxed for 2.5 hours. The mixture is cooled andfiltered,

and the filtrate concentrated. The residue is dissolved in ether, andthe solution filtered and concentrated to yield 900 mg. of residual oilwhich is further purified by chromatography on silica packed inn-hexane. Impurities are eluted using n-hexane-ether mixtures. Theproduct is selectively eluted with 50% ether in n-hexane to yield 0,0dibenzyl O {6-acetoxy-3,4-dihydro-2-methyl-2- (4,8,12'trimethyltridecyl) 2 H-naphthol[1,2-b] pyran- S-ylmethyl} phosphate,

Example 5 0,0 dibenzyl O(6-acetoxy-7,8-dimethoxy-2,2-dimethylchromand-ylmethyl)phosphate.An81-rng. portion of 5 chloromethyl 7,8-dimethoxy-2,2-dimethyl-6-chromanyl acetate is dissolved in 51ml. of toluene and and the ethersolution is washed once with very dilute wise until an excess of thereagent is present.

added to a suspension of 99 mg. of silver dibenzyl phosphate inapproximately 15 ml. of dry toluene.

The mixture is refluxed under nitrogen for approximately 17 hours. Thereaction mixture is cooled, and then filtered to remove precipitatedsilver chloride. The filtrate is washed with water, dried over sodiumsulfate and concentrated in vacuo. The residual oil is taken up inchloroform and the solution concentrated to remove traces of toluene,yielding a 12l-mg. residue. The infrared spectrum of the product showsthe expected bands at 3.35, 5.6, 6.7, 6.85, 7.0, 7.3, 8.25, 8.9, 9.6,and 9.8 The ultraviolet spectrum in 95% ethanol shows innx. l (Eiz (A imy shoulders at 258, 266, 270 mp).

Example 6 0,0-dibefizyl-O-{d-acetoxy 7,8 dimethoxy-Z-methyl-2-(4,8,1Z-trimethyltridecyl)chroman 5 ylmelhyl} phosphr'zte.-A 10-m1.portion of benzene is distilled from a suspension of 540 mg. of powderedsilver dibenzyl phos phate in 40 ml. of dry benzene. A solutioncontaining 540 mg. of 5-chloromethyl-7,8-dimethoxy-2-methyl-2-(4,8,12-trimethyltridecyl)-6-chromanyl acetate in 5 ml. of dry benzene isadded, and the mixture stirred and refluxed for 20 hrs. After beingcooled, the mixture is diluted with an equal volume of hexane, and theinsolubles removed by filtration. The filtrate is evaporated underreduced pressure giving 0,0-dibenzyl-O-{6-acetoxy- 7,8-dimethoxy '2methyl-2-(4,8,12 trimethyltridecyl) chroman-Sylmetl1yl}phosphate )riiiif290 m (Eii'g 34) xx; 5.64s, 6.30 s, 8.30 1, 8.99 99-101 and 14.35

Example 7 fate, filtered and concentrated; the residue is dissolved in asmall volume of petroleum ether. The product precipitated slowly, andafter several days, 6-acetoxy-3,4- dihydro-Z-methyl-Z-(4,3,12trimethyltridecyl)-2-H-naphtho[l,2-b]pyran-5-ylmethyldihydrogenphosphate is collected by centrifugation. The amorphousproduct is characterized by g t 1 N531. m 247 y lzim. max,

Example 8 0,0-dimethyl-O-{d-acetoxy 3,4 dihydro-Z-methyl-Z-(4,8,12-trimethyltridecyl) 2 H naphth0[1,2-b]pyran- 5-ylmethyl}ph0sphate.Twenty-six milligrams of 6-acetoxy-3,4-dihydro-2-"nethyl 2(4,8,12-trimethyltridecyl)- 2-H-naphtho[1,2-b]pyran 5 ylmethyldihydrogenphosphate is dissolved in a few ml. of ether and a solution offreshly prepared diazomethane in ether is added dropdiazomethane isdestroyed with a few drops of acetic acid,

potassium bicarbonate solution, and twice with water. The ether solutionis dried over anhydrous magnesium sulfate, filtered and concentrated invacuo to yield 0,0-

. dimethyl-O-{6-acetoxy-3,4-dihydro 2 methyl-2-(4,8,l2-'trimethyltridecyl) 2 H-naphtho[1,2-b]pyran-5-ylmethyl}dihydrogenphosphate as a colorless oil. The nuclear The excess gmagnetic resonance spectrum of the product is in accord with thestructure.

Example 9 6-acetoxy-7,8-dimeth0xy 2,2 dimethylchroman-S-ylmethyldihydrogenphosphate.A IZO-mg. portion of O, O-dibenzyl-O-(6 acetoxy 7,8dimethoxy-2,2-dimethylchroman-5-ylmethyl) phosphate is dissolved in 10ml. of pure dioxane and shaken under a hydrogen atmosphere at roomtemperature with 100 mg. of 10% palladium on carbon catalyst in 10 ml.of dioxane which had been preequilibrated with hydrogen. After about tenminutes the consumption of hydrogen becomes slow, and the reaction isstopped after 15 minutes. The mixture is filtered, and the filtrateconcentrated under vacuum to approximately l-ml. volume. The product isthen approximately neutralized with about one equivalent of 1 Npotassium hydroxide. The resulting solution is concentrated to drynessunder vacuum leaving a slightly yellow oily residue of the monopotassiumsalt of 6-acetoxy-7,8-dimethoxy- 2,2-dimethylchroman 5 ylmethyldihydrogenphosphate. The ultraviolet spectrum in 95% ethanol shows A 282mp,

(Ell...

(x 254.5 m The infrared spectrum in chloroform shows strong bands at3.4, 5.7, 6.9, 7.3, 8.6, and 8.9

The monopotassium salt is dissolved in Water and one equivalent ofhydrochloric acid added. The solution is then extracted with ether andthe ether extracts evaporated to obtain6-acetoxy-7,8-dimethoxy-2,2-dimethylchroman-S-ylmethyldihydrogenphosphate.

Example 10 6-acet0xy-7,8-dimeilz0xy 2methyl-2-(4,8,12-trimethyllridecyl)chrman 5 -ylmethyldihydrogenphosphate.-

Five hundred milligrams of 0,0-dibenzyl-O-{6-acet0xy-7,8-dimethoxy-2-methyl 2 (4,8,12-trimethyltridecyl)chroman-5-ylmethyl}phosphate is dissolved in 50 ml. of ethanol andhydrogenated at atmospheric pressure using 500 mg. of 5% palladium oncharcoal. The theoretical amount of hydrogen is consumer in 10 min. Thecatalyst is removed by filtration, and the filtrate evaporated underreduced pressure. The residue is dissolved in 50 ml. of 0.5 N potassiumbicarbonate, and the aqueous solution extracted with hexane, acidifiedwith m1. of 2 N hydrochloric acid, and extracted with ether. The ethersolution is diluted with benzene, separated from residual water andevaporated under reduced pressure to yield6-acetoxy-7,8-dimethoxy-2-methyl-2-(4,8,12-trimethyltridecyl)chroman-S-ylmethyldihydrogenphosphate:

Aim 289 mp (Eitm 43); 7.5:; 4.1-4.5,u, 5.65,, 6.30 8.301;, 8.9951, and9.851.

The structure of the product is confirmed by nuclear magnetic analysisof the dimethylphosphate ester derivative prepared by treatment of theproduct with diazomethane.

Example 11 The structure of the triester is confirmed by nuclearmagnetic spectroscopy.

& Example 12 5-acez0xymethyl-3,4 dihydro-2-methyl 2(4,8,I2-trimethyltria'ecyl) -2-H-naphth0[1,2b]pyran-6-yl acetate.- Amixture of 100 mg. of 5-chloromethyl-3,4-dihydro-2- methyl 2-(4,8,12trimethyltridecyl) 2-H naphtho[l, 2-b]pyran-6-yl acetate, 100 mg. ofsilver acetate and 5 ml. of acetic acid is refluxed for 30 minutes. Thereaction mixture is poured onto ice, and the product isolated byextraction with ether. The ether extract is dried over anhydrousmagnesium sulfate and concentrated. The residue is purified bypreparative thin-layer chromatography on silica usingisooctane-benZene-acctone 13 :2) to yield5-acetoxymethyl-3,4-dihydro-2-methyl-2-(4,8,12- trimethyltridecyl-2-H-naphtho[ 1,2-b] pyran-6-yl acetate, 11, (188-01:

MELT 247 u V-3m. 325.

Example 13 7,8-climeth0xy 6-hydr0xy Z-methyl 2-(4,8,12trimethyltridecyl) -chr0man 5 ylmethyl dihydrogenphosphate.Two hundredmilligrams of 2,3-dimethoxy-6-(3- hydroxy-3,7,11,15tetramethylhexadecyl)-5 methyl-1,4- benzoquinone is stirred with 4.65 g.of phosphoric acid prepared by mixing 3.4 g. of 85% phosphoric acid and1.25 g. of phosphorus pentoxide. The reaction mixture immediatelybecomes a homogeneous purple mass. After 10 minutes, the purple colorfades to a greenish black, and two phases start to separate. At the endof one hour, the reaction mixture is extracted with petroleum ether.Complete separation of the two phases is achieved by centrifugation. Thepetroleum ether extract is added directly to a column of silica gel inpetroleum ether, and the product is eluted with petroleum ether. Theeluate is extracted with several portions of water until the aqueousWash is neutral. The organic phase is then dried over anhydrous sodiumsulfate and concentrated under reduced pressure;7,8-dimethoxy-6-hydroxy-2-methyl-2-(4,8,12 trirnethyltridecyl)-chromanS-ylmethyl dihydrogenphosphate is obtained in this manner.

The new 5-phosphomethyl compounds of this invention in addition to beinguseful in the study of metabolic processes involving hydrogen transportand phosphorylation are also useful as antioxidants and as sun screeningagents. Thus, the compounds can be used in the preservation of chickensperm. They may also be used as antioxidants for oils and fats. Inaddition, since the phosphates absorb ultraviolet light rays, they couldbe used in the preparation of anti-sunburn preparations. Thesephosphorylated derivatives are superior to the non-phosphorylatedanalogs because salts of the phosphates can be prepared which permitimproved dispersion in aqueous vehicles. At the same time thesephosphates in the free form as well as certain salts also have certainsolubility in organic solvents because of their lipid characteristics.

Various changes and modifications of the invention can be made, and tothe extent that such variations incorporate the spirit of thisinvention, they are intended to be included within the scope of theappended claims.

What is claimed is:

1. The process which comprises reacting a 'y-hydroxy derivative of a1,4-quinone of the formula CH il l H O HO H3O R wherein Z is a memberfrom the group consisting of OHaO- catand I n V crno- CH3- and R is amember from the group consisting of methyl and wherein n is an integerfrom one to nine, with a halide from the group consisting of loweralkanoyl chlorides and bromides to produce a compound of the formulaOCOY.

wherein Z and R are defined as above, Y is lower allryl,

and X is a halogen from the group consisting of chlorin and bromine.

4. The process which comprises reacting 2,3-dimeth-' oxy 6 (3 hydroxy3,7,11,15 tetramethylhexadecyD- 5-rnethyl-1,4-benzoquinone with acetylchloride to produce 5 chloromethyl 7,8 dimethoxy 2 methyl 2- (4,8,12-trimethyltridecyl) -6-chrornany1 acetate.

5. A compound of the formula OOOY wherein Z is a member from the groupconsisting of cH3o ou and , cmoon,-

wherein n is an integer from one to nine, and X is a halogen from thegroup consisting of chlorine and bromine.

6. 5 chloromethyl 3,4 dihydro 2 methyl 2- (4,8,l2-trimethyltridecyl) 2 Hnaphtho[1,2-b]pyran-1 6-yl acetate.

7. 5 chloromethyl 7,8 dimethoxy 2,2 dimethyl-' G-chromanyl acetate.

l 8. 5 chloromethyl 7,8 dimethoxy 2 methyl 2- (4,8, 1Z-trirnethyltridecyl) -6-chromanyl acetate.

9. The process which comprises reacting a -hydroxy derivative of a1,4-quinone of the formula wherein Z is a member from the groupconsisting of and R is a member from the group consisting of methyl and.

wherein n is an integer from one. to nine, with a halide from the groupconsisting of lower alkanoyl chlorides and bromides, and intimatelycontacting the resulting reaction product withsilver dibenzyl phosphateto produce a compound of the formula wherein Z and R are the same asabove and Y is lower alkyl.

10. The process which comprises reacting 3 (3 -hydroxy 3,7,11,15:tetramethylhexadecyl) 2 methyll,4'-naphthoquinone with acetyl chlorideto produce 5- chloromethyl 3,4 dihydro 2 methyl 2 (4,8,12trimethyltridecyl) 2 H naphtho[1,2-b]pyran 6 yl acetate, and intimatelycontacting this product with silver dibenzyl phosphate to produce0,0-dibenzyl-O-{6-acetoxy 3,4 dihydro 2 methyl 2 (4,8,12trimethyltridecyl)-2-Hnaphtho[l,2-b]pyran 5 ylrnethyl} phosphate.

11. The process which comprises reacting 2,3-dirnethoxy 6 (3 hydroxy 3methylbutyl) 5 methyl 1,4-

benzoquinone with acetyl chloride to produce S-chloromethyl 7,8dimethoxy 2,2 dimethyl 6 chromanyl acetate, and intimately contactingthis product with silver dibenzyl phosphate to produce0,0-dibenzyl-O-(6-acetoxy 7,8 dimethoxy-Z,Z-dimethylchroman 5 ylmethylphosphate.

12. The process which comprises reacting 2,3-dimethoxy 6 (3 hydroxy3,7,11,15 tetramethylhexadecyl)- S-methyl-l,4-benzoquinone with acetylchloride to produce 5 chloromethyl 7,8 dimethoxy 2 methyl 2-(4,8,IZ-trimethyltridecyl)-6-chromanyl acetate, and intimatelycontacting this product with silver dibenzyl phosphate to produce0,0-dibenzyl-O-{6-acetoxy-7,8-dimethoxy 2 methyl 2 (4,8,12trimethyltridecyl)chroman- S-ylrnethyl} phosphate.

1 i 13. The process Which comprises intimately contacting a compound ofthe formula OCOY wherein Z is a member from the group consisting of OHO- and Y is lower alkyl, X is a halogen from the group consisting ofchlorine and bromine and R is a member from the group consisting ofmethyl and CH3 0H,, (CHgCH /H 2) nH wherein n is an integer from one tonine with silver dibenzyl phosphate to produce a compound of the formulaOCOY (I) OCI'I2CaI 01-1201 i 0011206115 H3O R wherein Z, Y and R are thesame as above.

14. A compound of the formula Y is lower alkyl, R is a member from thegroup consisting of benzyl and lower alkyl and R is a member from thegroup consisting of methyl and CH GH OH CH AEHCHQHH wherein n is aninteger from 1 to 9.

15. 0,0 dibenzyl-O-{6-acetoxy-3,4-dihydro-2-methyl- 2 (4,8,12-trimethyltridecyl)-2-H-naphtho[1,2-b1pyran- 5-ylmethyl} phosphate.

16. 0,0dibenzyl-O-{6-acetoXy-7,8-dimethoxy-2,2-dimethylch'roman-S-ylmethyl}phosphate.

17. 0,0dibenzyl-O-{6-acetoxy-7,8-dimeth0xy-2-methyl-2-(4,8,12-trirnethyltridecyl)chroman-S-ylmethyl}phosphate.

18. 0,0 dimethyl-O-{6-acetoXy-3,4-dihydro-2-methyl- 2 (4,8,12trimethyltridecyl)-2-H-naphtho[l,2-b]pyran- 5-ylmethyl} phosphate.

i. 2 19. The process which comprises reacting a compound of the formulawherein R is a member from the group consisting of methyl and wherein nis an integer from one to nine With phosphoric acid to produce acompound of the formula OCOY I o oomcnr,

ornor i 0011266115 H3O R wherein Z is a member from the group consistingof and Y is lower alkyl, and R is a member from the group consisting ofmethyl and (311:3 ormorr on orrofionn where n is an integer from one tonine with hydrogen in the presence of a noble metal catalyst to producethe corresponding dihydrogenphosphate compound.

22. A compound from the group consisting of compounds having the formula13 14 wherein Z is a member from the group consisting of 26. 6 hydroxy3,4 dihydro 2-methyl-2-(4,8,12-trimethyltridecyl)ZH-naphtho-[1,2-b1pyran-5-ylmethyl di- H3 H= hydrogenphosphate.

and 27. 6 hydroxy 7,8-dimethoxy-2,2-dimethylchromana s '5 5-yl1netl1yldihydrogenphosphate.

28. 6 hydroxy 7,8-dimethoxy-2-methyl-2-(4,8,12-tri- 18 a member from thegroup conslstmg of hydrogen methyltridecyl)chroman-S-ylmethyldihydrogenphosphate. and lower alkanoyl, and R is a member from thegroup consisting of methyl and References aired in the file of thispatent i 10 UNITED STATES PATENTS CHHCHWHZ EPOHWH 2,486,542 Weisler eta1. Nov. 1, 1949 wherein n is an integer from one to nine, and saltthereof. 3,026,330 Folkers et a1 Mar. 20, 1962 23. 6 acetoxy 3,4 dihydro2 methyl-2-(4,8,12-trimethyltridecyl) 2H-naphtho[1,2-b1pyran-5-ylmethyldi- FOREIGN PATENTS hydrogenphosphate. 826,640 Great Britain Jan. 13,1960 24. 6 acetoxy 7,8 dirnethoXy-Z,Z-dimethylchroman- 5-y1methyldihydrogenphosphate. OTHER REFERENCES 25. 6 acetoxy7,8-dimethoXy-2-methyl-2-(4,8,12-tri- Royals, Advanced OrganicChemistry, pp. 271, 604- methyltridecyl)chroman-S-ylmethyldihydrogenphosphate. 607, Prentice-Hall, Inc., Englewood Cliffs, NJ.(1956).

5. A COMPOUND OF THE FORMULA
 14. A COMPOUND OF THE FORMULA
 22. ACOMPOUND FROM THE GROUP CONSISTING OF COMPOUNDS HAVING THE FORMULA